title: A rat model of metastatic spinal cord compression using human prostate adenocarcinoma: histopathological and functional analysis.
abstract: BACKGROUND
  Cancer is a major global public health problem responsible for one in every four deaths in the United States. Prostate cancer alone accounts for 29% of all cancers in men and is the sixth leading cause of death in men. It is estimated that up to 30% of patients with cancer will develop metastatic disease, the spine being one of the most frequently affected sites in patients with prostate cancer.
  
  
  OBJECTIVE
  To study this condition in a preclinical setting, we have created a novel animal model of human metastatic prostate cancer to the spine and have characterized it histologically, functionally, and via bioluminescence imaging.
  
  
  METHODS
  Translational science investigation of animal model of human prostate cancer in the spine.
  
  
  METHODS
  Luciferase-positive human prostate tumor cells PC3 (PC3-Luc) were injected in the flank of athymic male rats. PC3-Luc tumor samples were then implanted into the L5 vertebral body of male athymic rats (5 weeks old). Thirty-two rats were randomized into three surgical groups: experimental, control, and sham. Tumor growth was assessed qualitatively and noninvasively via bioluminescence emission, upon luciferin injection. To determine the functional impact of tumor growth in the spine, rats were evaluated for gait abnormalities during gait locomotion using video-assisted gait analysis. Rats were euthanized 22 days after tumor implantation, and spines were subjected to histopathological analyses.
  
  
  RESULTS
  Twenty days after tumor implantation, the tumor-implanted rats showed distinct signs of gait disturbances: dragging tail, right- or left-hind limb uncoordination, and absence of toe clearance during forward limb movement. At 20 days, all rats experienced tumor growth, evidenced by bioluminescent signal. Locomotion parameters negatively affected in tumor-implanted rats included stride length, velocity, and duration. At necropsy, all spines showed evidence of tumor growth, and the histological analysis found spinal cord compression and peritumoral osteoblastic reaction characteristic of bony prostate tumors. None of the rats in the sham or control groups demonstrated any evidence of bioluminescence signal or signs of gait disturbances.
  
  
  CONCLUSIONS
  In this project, we have developed a novel animal model of metastatic spine cancer using human prostate cancer cells. Tumor growth, evaluated via bioluminescence and corroborated by histopathological analyses, affected hind limb locomotion in ways that mimic motor deficits present in humans afflicted with metastatic spine disease. Our model represents a reliable method to evaluate the experimental therapeutic approaches of human tumors of the spine in animals. Gait locomotion and bioluminescence analyses can be used as surrogate noninvasive methods to evaluate tumor growth in this model.
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Meyer 7-109, Baltimore, MD 21287, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sarabia-Estrada
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Zadnik
authors.forename: Camilo A
authors.initials: CA
authors.lastname: Molina
authors.forename: Ismael
authors.initials: I
authors.lastname: Jimenez-Estrada
authors.forename: Mari L
authors.initials: ML
authors.lastname: Groves
authors.forename: Ziya L
authors.initials: ZL
authors.lastname: Gokaslan
authors.forename: Ali
authors.initials: A
authors.lastname: Bydon
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Witham
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Wolinsky
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sciubba
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000556:secondary*; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005684:Gait; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000150:complications / Q000473:pathology*; D051381:Rats; D013117:Spinal Cord Compression / Q000209:etiology / Q000473:pathology*; D013125:Spinal Neoplasms / Q000556:secondary*
keywords: Animal gait locomotion; Animal model; Metastatic prostate cancer; Spinal metastasis; Spine tumor